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Key Points A risk score model (BATAP) was established to facilitate the prognostic stratification of patients with TA-TMA following allo-HSCT.The BATAP prognostic model showed robust predictive capacity through internal and external temporal validation., Visual Abstract, Transplant-associated thrombotic microangiopathy (TA-TMA) is a potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Information on markers for early prognostication remains limited, and no predictive tools for TA-TMA are available. We attempted to develop and validate a prognostic model for TA-TMA. A total of 507 patients who developed TA-TMA following allo-HSCT were retrospectively identified and separated into a derivation cohort and a validation cohort, according to the time of transplantation, to perform external temporal validation. Patient age (odds ratio [OR], 2.371; 95% confidence interval [CI], 1.264-4.445), anemia (OR, 2.836; 95% CI, 1.566-5.138), severe thrombocytopenia (OR, 3.871; 95% CI, 2.156-6.950), elevated total bilirubin (OR, 2.716; 95% CI, 1.489-4.955), and proteinuria (OR, 2.289; 95% CI, 1.257-4.168) were identified as independent prognostic factors for the 6-month outcome of TA-TMA. A risk score model termed BATAP (Bilirubin, Age, Thrombocytopenia, Anemia, Proteinuria) was constructed according to the regression coefficients. The validated c-statistic was 0.816 (95%, CI, 0.766-0.867) and 0.756 (95% CI, 0.696-0.817) for the internal and external validation, respectively. Calibration plots indicated that the model-predicted probabilities correlated well with the actual observed frequencies. This predictive model may facilitate the prognostication of TA-TMA and contribute to the early identification of high-risk patients.

Copper/zinc superoxide dismutase (SOD1) can clear cisplatin- (CP-) induced excessive reactive oxygen species (ROS), but exogenous SOD1 cannot enter cells because of its low biomembrane permeability. Cell-penetrating peptides (CPPs) can rapidly cross plasma membranes. This study is aimed at identifying an efficient and stable CPP-SOD1 and investigating its effects on CP-induced nephrotoxicity. We recombined SOD1 with 14 different CPPs and purified them using an NTA-Ni2+ column. In in vitro experiments, CPPs-SOD1 cell membrane penetration ability and JNK/p38 MAPK signaling pathway were evaluated using Western blotting. ROS production, mitochondrial membrane potential (MMP), and cell apoptosis were determined using flow cytometry and immunofluorescence staining in VERO and HK-2 cells. For in vivo experiments, mice were administered PSF-SOD1 for 2 h before cotreatment with a single CP injection for an additional 4 days. Blood and kidney samples were collected for renal function assessment (creatinine, urea nitrogen, histopathology, TUNEL assay, and JNK/p38 MAPK signaling pathway). Compared with TAT-SOD1, we found that PSF-SOD1 is more efficient at crossing the cell membrane and is stable after transduction into cells. Pretreatment with PSF-SOD1 inhibited CP-induced apoptosis, ROS generation, and JNK/p38 MAPK activation and restored CP-induced MMP loss in VERO and HK-2 kidney cells. Treatment of mice with PSF-SOD1 inhibited CP-induced serum creatinine, blood urea nitrogen elevation, and JNK/p38 MAPK activation. H&E staining and TUNEL assay indicated that kidney tissue damage was alleviated following PSF-SOD1 pretreatment. Overall, PSF-SOD1 ameliorated CP-induced renal damage by partially reducing oxidative stress and cell apoptosis by regulating JNK/p38 MAPK signaling pathway and might be a better cytoprotective agent than TAT-SOD1.

The sudden emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) has caused global panic in 2003, and the risk of SARS-CoV outbreak still exists. However, no specific antiviral drug or vaccine is available; thus, the development of therapeutic antibodies against SARS-CoV is needed. In this study, a nanobody phage-displayed library was constructed from peripheral blood mononuclear cells of alpacas immunized with the recombinant receptor-binding domain (RBD) of SARS-CoV. Four positive clones were selected after four rounds of bio-panning and subjected to recombinant expression in E. coli. Further biological identification demonstrated that one of the nanobodies, S14, showed high affinity to SARS-CoV RBD and potent neutralization activity at the picomole level against SARS-CoV pseudovirus. A competitive inhibition assay showed that S14 blocked the binding of SARS-CoV RBD to either soluble or cell-expressed angiotensin-converting enzyme 2 (ACE2). In summary, we developed a novel nanobody targeting SARS-CoV RBD, which might be useful for the development of therapeutics against SARS.

Coencapsulation of chemotherapeutic agents and photosensitizers into nanocarriers can help to achieve a combination of chemotherapy and photodynamic therapy for superior antitumor effects. However, precise on-demand drug release remains a major challenge. In addition, the loaded photosensitizers usually tend to aggregate, which can significantly weaken their fluorescent signals and photodynamic activities. To address these issues, herein, a smart nanocarrier termed as singlet oxygen-responsive nanoparticle (SOR-NP) was constructed by introducing singlet oxygen (1O2)-sensitive aminoacrylate linkers into amphiphilic mPEG-b-PCL copolymers. Boron dipyrromethene (BDP) and paclitaxel (PTX) as model therapeutic agents were coloaded into an 1O2-responsive nanocarrier for realizing light-controlled drug release and combination cancer treatment. This polymeric nanocarrier could substantially relieve the aggregation of encapsulated BDP due to the presence of a long hydrophobic chain. Therefore, the formed SOR-NPBDP/PTX nanodrug could generate bright fluorescent signals and high levels of 1O2, which could mediate cell death via PDT and rupture aminoacrylate linker simultaneously, leading to collapse of SOR-NPBDP/PTX and subsequent PTX release. The light-triggered drug release and combined anticancer effects of SOR-NPBDP/PTX were validated in HepG2 and MCF-7 cancer cells and H22 tumor-bearing mice. This study provides a promising strategy for tumor-specific drug release and selective photodynamic-chemo combination treatment.

Background:. Acute heart failure (AHF) is the most common disease in emergency departments (EDs). However, clinical data exploring the outcomes of patients presenting AHF in EDs are limited, especially the long-term outcomes. The purposes of this study were to describe the long-term outcomes of patients with AHF in the EDs and further analyze their prognostic factors. Methods:. This prospective, multicenter, cohort study consecutively enrolled 3335 patients with AHF who were admitted to EDs of 14 hospitals from Beijing between January 1, 2011 and September 23, 2012. Kaplan-Meier and Cox regression analysis were adopted to evaluate 5-year outcomes and associated predictors. Results:. The 5-year mortality and cardiovascular death rates were 55.4% and 49.6%, respectively. The median overall survival was 34 months. Independent predictors of 5-year mortality were patient age (hazard ratio [HR]: 1.027, 95 confidence interval [CI]: 1.023–1.030), body mass index (BMI) (HR: 0.971, 95% CI: 0.958–0.983), fatigue (HR: 1.127, 95% CI: 1.009–1.258), ascites (HR: 1.190, 95% CI: 1.057–1.340), hepatic jugular reflux (HR: 1.339, 95% CI: 1.140–1.572), New York Heart Association (NYHA) class III to IV (HR: 1.511, 95% CI: 1.291–1.769), heart rate (HR: 1.003, 95% CI: 1.001–1.005), diastolic blood pressure (DBP) (HR: 0.996, 95% CI: 0.993–0.999), blood urea nitrogen (BUN) (HR: 1.014, 95% CI: 1.008–1.020), B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in the third (HR: 1.426, 95% CI: 1.220–1.668) or fourth quartile (HR: 1.437, 95% CI: 1.223–1.690), serum sodium (HR: 0.980, 95% CI: 0.972–0.988), serum albumin (HR: 0.981, 95% CI: 0.971–0.992), ischemic heart diseases (HR: 1.195, 95% CI: 1.073–1.331), primary cardiomyopathy (HR: 1.382, 95% CI: 1.183–1.614), diabetes (HR: 1.118, 95% CI: 1.010–1.237), stroke (HR: 1.252, 95% CI: 1.121–1.397), and the use of diuretics (HR: 0.714, 95% CI: 0.626–0.814), β-blockers (HR: 0.673, 95% CI: 0.588–0.769), angiotensin-converting enzyme inhibitors (ACEIs) (HR: 0.714, 95% CI: 0.604–0.845), angiotensin-II receptor blockers (ARBs) (HR: 0.790, 95% CI: 0.646–0.965), spironolactone (HR: 0.814, 95% CI: 0.663–0.999), calcium antagonists (HR: 0.624, 95% CI: 0.531–0.733), nitrates (HR: 0.715, 95% CI: 0.631–0.811), and digoxin (HR: 0.579, 95% CI: 0.465–0.721). Conclusions:. The results of our study demonstrate poor 5-year outcomes of patients presenting to EDs with AHF. Age, BMI, fatigue, ascites, hepatic jugular reflux, NYHA class III to IV, heart rate, DBP, BUN, BNP/NT-proBNP level in the third or fourth quartile, serum sodium, serum albumin, ischemic heart diseases, primary cardiomyopathy, diabetes, stroke, and the use of diuretics, β-blockers, ACEIs, ARBs, spironolactone, calcium antagonists, nitrates, and digoxin were independently associated with 5-year all-cause mortality.

Background: Human growth hormone (hGH) is the first recombinant protein approved for the treatment of human growth hormone deficiency. However, expression in inclusion bodies and low expression levels are enormous challenges for heterologous expression of hGH in Escherichia coli. Objective: To increase the soluble expression of recombinant hGH with correct folding in E. coli. Methods: We constructed a new recombinant expression plasmid containing the coding sequence of the outer membrane protein A (ompA3) which was used for the expression in Transetta (DE3) E. coli. In order to simplify the purification process and cleavage of recombinant proteins, the fusion sequence should contain hexahistidine-tag (His6) and enterokinase recognition sites (D4K). The effect of different expression conditions on recombinant hGH expression was optimized in flask cultivations. Furthermore, the periplasmic solution containing soluble hGH was purified by Ni-NTA affinity chromatography. Circular dichroism (CD), western blot and mass spectrometry analyses were used to characterize the protein. Moreover, the growth-promoting effect of the purified hGH was also evaluated by cell proliferation assay. Results: High-level expression (800 g/mL) was achieved by induction with 0.5 mM IPTG at 30 ºC for 10 hours. The purity of hGH was over 90%. The immunological activity, secondary structure and molecular weight of the purified hGH were consistent with native hGH. The purified hGH was found to promote the growth of MC3T3-E1 cells, and was found to show the highest activity at a concentration of 100 ng/mL. Conclusion: Our research provides a feasible and convenient method for the soluble expression of recombinant hGH in E. coli, and may lay a foundation for the production and application of hGH in the industry.

Despite advances in screening and treatment, colon cancer remains one of the leading causes of cancer-related death. Finding novel and useful drug treatment targets is also an urgent need for clinical applications. Tetrandrine (Tet) is extracted from the Chinese medicinal herbal medicine, which is a well-known calcium blocker with a variety of pharmacological activities, including anti-cancer. In this study, we recruited cell viability assay, flow cytometry analysis, cloning formation to confirm that Tet can inhibit the proliferation of SW620 cells, and induce apoptosis. Mechanically, we confirmed that Tet up-regulates the mRNA and protein level of BMP9 in SW620 cells. Over-expression BMP9 enhances the anti-cancer effects of Tet in SW620 cells, but these effects can be partly reversed by silencing BMP9. Also, Tet reduces phosphorylation of Aktl/2/3 in SW620 cells, which could be elevated by overexpressed BMP9 and impaired by silencing BMP9. Furthermore, we demonstrated that Tet reduces phosphorylated PTEN, which can be promoted by overexpressed BMP9, analogously also be attenuated through silencing BMP9. Finally, we introduced a xenograft tumor model to investigate the anti-proliferative effect of Tet, further to explore the effects of BMP9 and PTEN in SW620 cells. Our findings suggested that the anti-cancer activity of Tet in SW620 cells may be mediated partly by up-regulating BMP9, followed by inactivation PI3K/Akt through up-regulating PTEN at least.

We use satellite (GOSAT) and in situ (GLOBALVIEWplus CH4 ObsPack) observations of atmospheric methane in a joint global inversion of methane sources, sinks, and trends for the 2010–2017 period. The inversion is done by analytical solution to the Bayesian optimization problem, yielding closed-form estimates of information content to assess the consistency and complementarity (or redundancy) of the satellite and in situ data sets. We find that GOSAT and in situ observations are to a large extent complementary, with GOSAT providing a stronger overall constraint on the global methane distributions, but in situ observations being more important for northern midlatitudes and for relaxing global error correlations between methane emissions and the main methane sink (oxidation by OH radicals). The in-situ-only and the GOSAT-only inversions alone achieve 113 and 212 respective independent pieces of information (DOFS) for quantifying mean 2010–2017 anthropogenic emissions on 1009 global model grid elements, and respective DOFS of 67 and 122 for 2010–2017 emission trends. The joint GOSAT+ in situ inversion achieves DOFS of 262 and 161 for mean emissions and trends, respectively. Thus, the in situ data increase the global information content from the GOSAT-only inversion by 20 %–30 %. The in-situ-only and GOSAT-only inversions show consistent corrections to regional methane emissions but are less consistent in optimizing the global methane budget. The joint inversion finds that oil and gas emissions in the US and Canada are underestimated relative to the values reported by these countries to the United Nations Framework Convention on Climate Change (UNFCCC) and used here as prior estimates, whereas coal emissions in China are overestimated. Wetland emissions in North America are much lower than in the mean WetCHARTs inventory used as a prior estimate. Oil and gas emissions in the US increase over the 2010–2017 period but decrease in Canada and Europe. The joint inversion yields a global methane emission of 551 Tg a−1 averaged over 2010–2017 and a methane lifetime of 11.2 years against oxidation by tropospheric OH (86 % of the methane sink).

The corrosion behavior of pure copper exposed to the atmosphere of Nansha Islands for 21 months was studied by mass loss method, composition analysis, morphology observation and electrochemical measurements. The results showed that the average corrosion rate of copper exposed for one year was approximately 7.85 μm/a, implying that Nansha Islands was classified as a corrosion category of CX. The structure and properties of the corrosion product layer generated on the front and back sides of the exposed sample differed significantly. The inner corrosion product layer (Cu2O) on the front side was relatively thick and dense, whereas the outer product layer (Cu2Cl(OH)3) was extremely thin. However, the outer product layer on the back side was thicker than the inner layer. Electrochemical measurements indicated that the protection afforded by the corrosion product layer on the front side was improved gradually, while that on the back side was deteriorated.

Surface ozone is a major pollutant in eastern China, especially during the summer season. The formation of surface ozone pollution highly depends on meteorological conditions largely controlled by regional circulation patterns which can modulate ozone concentrations by influencing the emission of the precursors, the chemical production rates, and regional transport. Here we show that summertime ozone pollution over eastern China is distinctly modulated by the variability of the western Pacific subtropical high (WPSH), a major synoptic system that controls the summertime weather conditions of East Asia. Composite and regression analyses indicate that a positive WPSH anomaly is associated with higher than normal surface ozone concentration over northern China but lower ozone over southern China. Stronger than normal WPSH leads to higher temperatures, stronger solar radiation at the land surface, lower relative humidity, and less precipitation in northern China, favoring the production and accumulation of surface ozone. In contrast, all meteorological variables show reverse changes in southern China under a stronger WPSH. GEOS-Chem simulations reasonably reproduce the observed ozone changes associated with the WPSH and support the statistical analyses. We further conduct a budget diagnosis to quantify the detailed contributions of chemistry, transport, mixing, and convection processes. The result shows that chemistry plays a decisive role in leading the ozone changes among these processes. Results show that the changes in ozone are primarily attributed to chemical processes. Moreover, the natural emission of precursors from biogenic and soil sources, a major component influencing the chemical production, accounts for ∼ 30 % of the total surface ozone changes.

Dimethyl sulfoxide (DMSO) is a universally used solvent in various synthetic reactions, and trace amounts of DMSO residual are often seen on the surface of chemical product. It is difficult to quickly determine whether the residual DMSO is washed completely. This work reports a CdII metal-organic framework (MOF) SXU-4 which can detect trace amounts of DMSO in various solvents. Fluorescence experiments reveal its turn-on fluorescence effect toward DMSO with high selectivity and sensitivity, indicating that it can be used as an effective luminescent probe for rapid chemical product purity detection by testing the washing solution. Crystallographically characterized DMSO loaded SXU-4 (DMSO@SXU-4), in combination with computational results uncover that the enhanced DMSO-MOF conjugation through multiple DMSO-MOF supramolecule interactions and charge rearrangement are the main causes of fluorescence intensification.

Electrochemical nitrogen reduction reactions (NRRs) show great potential for replacing the energy-intensive Haber–Bosch process, but require highly active electrocatalytic centers. Although various catalysts have been recently developed for NRRs, their inefficiency remained a huge obstacle for further commercialization. In this work, a shell-engineering strategy is proposed for the design of iron-doped titanium dioxide hollow nanospheres (FeHTNs) with abundant oxygen vacancies for NRRs based on the breathing process of mammalian alveolus. The hollow structure and porous shell of FeHTNs enable fast delivery of N2 reactants into the cavity of “alveolus” and stay in there longer and thus give N2 molecules more chance to contact the inner surface of electrocatalysts and hence greatly enhance NRR kinetics for the formation of ammonia. The dissolved ammonia in the electrolytic solution, in turn, creates negative pressure in cavities, which can suck N2 reactants automatically into the cavity, triggering the “domino effect” for continuous NRRs. A record ammonia yield of 43.14 μg h−1 mgcat.−1 at −0.7 V vs. RHE was achieved on Fe1.0HTN catalysts, close to the top of the pyramid among recently reported TO2-based catalysts. Besides, Fe1.0HTNs were employed as a N2 cathode for assembled Zn–N2 aqueous batteries, achieving both ammonia production (average NH3 yield: 0.172 μg h−1 cm−2) and electricity generation (power density: 16.42 μW cm−2), which offers a fascinating prospect for practical applications.

Objective: Determine the effect of interleukin (IL)-15 on HTR-8/SVneo cells and a preeclampsia (PE) mouse model induced by LPS. Methods: Transwell and Annexin-V-FITC/PI assays were performed in HTR-8/SVneo cells transfected with IL-15 activation plasmid/siRNA prior to LPS treatment. Additionally, pregnant mice were injected with LPS and IL-15 siRNA followed by measurement of systolic blood pressure (SBP), urine protein, and serum NO. HE staining was used to observe the morphological changes of the placenta and kidney. Glycogen accumulation was detected using Best’s carmine. qRT-PCR, Western blotting, and ELISA were performed to detect mRNA and protein expression. Results: LPS increased IL-15 and IFN-γ expression in HTR-8/SVneo cells, and IL-15 positively regulated IFN-γ expression in LPS-induced HTR-8/SVneo cells. Moreover, LPS promoted apoptosis and reduced the invasion and migration of HTR-8/SVneo cells, which was, further, promoted by IL-15 overexpression but attenuated by IL-15 inhibition. Furthermore, LPS increased SBP and urine protein but decreased serum NO in mice, and these factors were reversed by IL-15 siRNA. Downregulation of IL-15 also mitigated kidney injury and improved pregnancy outcomes in LPS-induced PE mice. A significantly thicker junctional zone (JZ) and thinner labyrinth layer were found in placentas of PE mice treated with IL-15 siRNA, along with increased glycogen trophoblast cells in the JZ. Moreover, decreased IFN-γ and NKp46 were found in placentas of PE mice treated with IL-15 siRNA. Conclusion: IL-15 inhibition reduced cell apoptosis and increased the invasive and migratory abilities of LPS-induced HTR-8/SVneo cells, thereby alleviating the PE-like phenotype and improving pregnancy outcome.

Pueraria lobata is utilized as a food source in China. The aim of this study is to combine virtual screening and molecular dynamics predictive model to screen out the potential synaptic plasticity-maintaining components from the root of P. lobate and to verify it by employing the amyloid β-injected rats' model. Eighteen compounds were identified by HPLC-MS/MS; puerarin manifested the most potential to form a stable complex with calcium/calmodulin kinase IIα (CaMK IIα), which is the key protein in synaptic plasticity by the in silico study. The further in vivo assay showed that puerarin could elevate the synaptic thickness, density, and length, relieve calcium overload, regulate the expression of CaMK IIα, and other p38MAPK-CREB signaling pathway-related biochemical criteria. The behavioral test also verified the results. Results have confirmed that the root of P. lobate can work anti-AD by maintaining the synaptic plasticity and proved the reliability of using the in silico predictive model to determine active ingredients from the natural product.

Gastric cancer (GC) is a major global cancer burden, and only HER2-targeted therapies have been approved in first line clinical therapy. CLDN18.2 has been regarded as a potential therapeutic target for gastrointestinal tumors, and global clinical trials have been in process. Hence, the precise, efficient, and noninvasive detection of CLDN18.2 expression is important for the effective application of this attractive target. A high similarity of protein sequence between CLDN18.1 and -18.2 made RNA become more suitable for the detection of CLDN18.2 expression. In this study, CLDN18.2 molecular beacon (MB) with a stem-loop hairpin structure was optimized by phosphorothioate and 2'-O-methyl for stability and efficiency. The MB could recognize CLDN18.2 RNA rapidly. Its resolution and selectivity has been verified in several model cells, demonstrating that MB can distinguish CLDN18.2 expression in several model cells. Furthermore, it was applied successfully to the circulating tumor cell (CTC) assay. The concordance in the expression of CLDN18.2 between CTCs and tissue biopsy is 100% (negative: 3 vs 3; positive: 7 vs 7), indicating that CLDN18.2 RNA detection in CTCs based on a MB will be a promising approach for searching potential patients to CLDN 18.2 targeted drug.

The Grubbs–Hoveyda catalysts have a wide range of applications in catalyzed formation of the carbon-carbon double bonds. In this study, several imidazolium- functionalized or pyridinium-functionalized silver carboxylates have been prepared, and their reaction with Grubbs–Hoveyda 2nd generation (G–H 2nd) catalyst leads a new type of processes. Activity and selectivity of the catalysts have been preliminarily evaluated using cross olefin metathesis reactions.

Drug resistance is a constant threat to malaria control efforts making it important to maintain a good pipeline of new drug candidates. Of particular need are compounds that also block transmission...

In order to better understand why the corrosion behavior of carbon steel exposed in Nansha atmospheric environment is very serious, the effect of sodium, potassium and magnesium chlorides deposited on carbon steel surface has been studied under atmosphere conditions by wet/dry accelerated test. The difference of corrosion behavior and surface structure in Na+, K+, and Mg2+ containing atmosphere has been investigated by thickness loss, scanning electron microscope, X-ray diffraction and electrochemical techniques. The results indicate that the thickness loss of carbon steel exposed in different metal cations containing atmospheric environment increases in the order of Na+, K+, Mg2+. The hard metal cation can promote the dissolution of the steel to a certain extent. In Mg2+ containing atmosphere, the relative content of β-FeOOH is rather higher and the protective ability index α*/γ* decreases in the order of Na+, K+, Mg2+. The corrosion current density of both bare carbon steel and the rusted carbon steel increases in the order of Na+, K+, Mg2+. The polarization resistance and the charge transfer resistance decreases in the order of Na+, K+, Mg2+.

Self-assembly of divalent metal ions and designed amino acid derivatives, 4,4′-biphenyl-bis[carbonyl-N-(alanine)] (H2BPBAla) and 4,4′-biphenyl-bis[carbonyl-N-(proline)] (H2BPBPro), as well as ancil...

China’s nationwide ozone monitoring network initiated in 2013 has observed severe surface ozone pollution. This network, combined with the recent Tropospheric Ozone Assessment Report (TOAR) data set, offers a more comprehensive view on global surface ozone distribution and trends. Here, we report quantitative estimates of the warm-season (April–September) surface ozone trends and resulting health impacts at Chinese cities in 2013–2019. Both the parametric and nonparametric linear trends for 12 ozone metrics relevant to human health and vegetation exposure are derived. We find that all ozone metrics averaged from Chinese urban sites have increased significantly since 2013. The warm-season daily maximum 8-h average (MDA8) ozone levels increased by 2.4 ppb (5.0%) year–¹, with over 90% of the sites showing positive trends and 30% with trends larger than 3.0 ppb year–¹. These rates are among the fastest trends, even faster in some Chinese cities, compared with the urban ozone trends in any other region worldwide reported in TOAR. Ozone metrics reflecting the cumulative exposure effect on human health and vegetation such as SOMO35 and AOT40 have increased at even faster rates (>10% year–¹). We estimate that the total premature respiratory mortalities attributable to ambient MDA8 ozone exposure in 69 Chinese cities are 64,370 in 2019, which has increased by 60% compared to 2013 levels and requires urgent attention.

Nitrogen fixation via the electrochemical nitrogen reduction reaction under ambient conditions has the potential to disrupt the energy-intensive Haber–Bosch process with a more environmentally friendly alternative. Utilizing air as the feed stock would represent an important step towards future industrialization of green ammonia. Herein, a gold–copper nanoalloy-decorated zeolitic imidazolate framework, denoted as AuCu/ZIF-8, exhibits high NH3 yield, remarkable efficiency, long-term stability and pH independence for the electrochemical synthesis of ammonia. Making ammonia from thin air and renewable electricity speaks well for the development of sustainable ammonia refineries.

Zinc finger proteins are widely involved and play an important role in plant growth and abiotic stress. In this research, MdZAT5, a gene encoding C2H2-type zinc finger protein, was cloned and investigated. The MdZAT5 was highly expressed in flower tissues by qRT-PCR analyses and GUS staining. Promoter analysis showed that MdZAT5 contained multiple response elements, and the expression levels of MdZAT5 were induced by various abiotic stress treatments. Overexpression of MdZAT5 in apple calli positively regulated anthocyanin accumulation by activating the expressions of anthocyanin biosynthesis-related genes. Overexpression of MdZAT5 in Arabidopsis also enhanced the accumulation of anthocyanin. In addition, MdZAT5 increased the sensitivity to salt stress in apple calli. Ectopic expression of MdZAT5 in Arabidopsis reduced the expression of salt-stress-related genes (AtNHX1 and AtABI1) and improved the sensitivity to salt stress. In conclusion, these results suggest that MdZAT5 plays a positive regulatory role in anthocyanin accumulation and negatively regulates salt resistance.

Proper metabolic activities facilitate T cell expansion and antitumor function; however, the mechanisms underlying disruption of the T cell metabolic program and function in the tumor microenvironment (TME) remain elusive. Here, we show a zinc finger protein 91–governed (ZFP91-governed) mechanism that disrupts the metabolic pathway and antitumor activity of tumor-infiltrating T cells. Single-cell RNA-Seq revealed that impairments in T cell proliferation and activation correlated with ZFP91 in tissue samples from patients with colorectal cancer. T cell–specific deletion of Zfp91 in mice led to enhanced T cell proliferation and potentiated T cell antitumor function. Loss of ZFP91 increased mammalian target of rapamycin complex 1 (mTORC1) activity to drive T cell glycolysis. Mechanistically, T cell antigen receptor–dependent (TCR-dependent) ZFP91 cytosolic translocation promoted protein phosphatase 2A (PP2A) complex assembly, thereby restricting mTORC1-mediated metabolic reprogramming. Our results demonstrate that ZFP91 perturbs T cell metabolic and functional states in the TME and suggest that targeting ZFP91 may improve the efficacy of cancer immunotherapy.

The recurrent outbreak of coronaviruses and variants underscores the need for broadly reactive antivirals and vaccines. Here, a novel broad-spectrum human antibody named 76E1 was isolated from a COVID-19 convalescent patient and showed broad neutralization activity against multiple α- and β-coronaviruses, including the SARS-CoV-2 variants and also exhibited the binding breath to peptides containing the epitope from γ- and δ- coronaviruses. 76E1 cross-protects mice from SARS-CoV-2 and HCoV-OC43 infection in both prophylactic and treatment models. The epitope including the fusion peptide and S2’ cleavage site recognized by 76E1 was significantly conserved among α-, β-, γ- and δ- coronaviruses. We uncovered a novel mechanism of antibody neutralization that the epitope of 76E1 was proportionally less exposed in the prefusion trimeric structure of spike protein but could be unmasked by binding to the receptor ACE2. Once the epitope exposed, 76E1 inhibited S2’ cleavage, thus blocked the membrane fusion process. Our data demonstrate a key epitope targeted by broadly-neutralizing antibodies and will guide next-generation epitope-based pan-coronavirus vaccine design.

Objective The goal of the present study was to observe the effect of autophagy in tibial plateau chondrocytes on apoptosis in spontaneous knee osteoarthritis (OA) in guinea pigs. Design Fifty 2-month-old female Hartley guinea pigs were divided into a normal group (10 animals, all euthanized after 7 months) and an OA group (40 animals, 10 of which were euthanized after 10 months). Immunohistochemistry, RT-qPCR and Western blotting were used to evaluate autophagy levels, intracellular glycogen accumulation and apoptosis in tibial plateau chondrocytes in vivo and in vitro. The remaining 30 guinea pigs in the OA group were divided into 3 groups: a rapamycin group, a normal saline group, and a 3-methyladenine (3-MA) group. Intracellular glycogen accumulation and chondrocyte apoptosis were assessed by altering the level of autophagy in chondrocytes in vivo. Results When spontaneous OA occurred in guinea pigs, autophagy levels in tibial plateau chondrocytes decreased, while intracellular glycogen accumulation and the rate of chondrocyte apoptosis increased. After enhancing the level of autophagy in tibial plateau chondrocytes in guinea pigs with OA, intracellular glycogen accumulation and the rate of chondrocyte apoptosis decreased, while inhibiting autophagy had the opposite effects. Conclusion The results indicate that the function of autophagy in chondrocytes may at least partly involve the catabolism of glycogen. In guinea pigs with OA, the level of autophagy in tibial plateau chondrocytes decreased, and chondrocytes were unable to degrade intracellular glycogen into glucose, leading to less energy for chondrocytes and increased apoptosis.

BackgroundSpinal cord ischemia reperfusion injury (SCIRI) is a complication of aortic aneurysm repair or spinal cord surgery that is associated with permanent neurological deficits. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have been shown to be potential therapeutic options for improving motor functions after SCIRI. Due to their easy access and multi-directional differentiation potential, adipose‐derived stem cells (ADSCs) are preferable for this application. However, the effects of ADSC-derived sEVs (ADSC-sEVs) on SCIRI have not been reported.ResultsWe found that ADSC-sEVs inhibited SCIRI induced neuronal apoptosis, degradation of tight junction proteins and suppressed endoplasmic reticulum (ER) stress. However, in the presence of the ER stress inducer, tunicamycin, its anti-apoptotic and blood-spinal cord barrier (BSCB) protective effects were significantly reversed. We found that ADSC-sEVs contain tumor necrosis factor-(TNF) stimulated gene-6 (TSG-6) whose overexpression inhibited ER stress in vivo by modulating the PI3K/AKT pathway.ConclusionsADSC-sEVs inhibit neuronal apoptosis and BSCB disruption in SCIRI by transmitting TSG-6, which suppresses ER stress by modulating the PI3K/AKT pathway.

Pathologically, blood-spinal-cord-barrier (BSCB) disruption after spinal cord injury (SCI) leads to infiltration of numerous peripheral macrophages into injured areas and accumulation around newborn vessels. Among the leaked macrophages, M1-polarized macrophages are dominant and play a crucial role throughout the whole SCI process. The aim of our study was to investigate the effects of M1-polarized bone marrow-derived macrophages (M1-BMDMs) on vascular endothelial cells and their underlying mechanism. Microvascular endothelial cell line bEnd.3 cells were treated with conditioned medium or exosomes derived from M1-BMDMs, followed by evaluations of endothelial-to-mesenchymal transition (EndoMT) and mitochondrial function. After administration, we found conditioned medium or exosomes from M1-BMDMs significantly promoted EndoMT of vascular endothelial cells in vitro and in vivo, which aggravated BSCB disruption after SCI. In addition, significant dysfunction of mitochondria and accumulation of reactive oxygen species (ROS) were also detected. Furthermore, bioinformatics analysis demonstrated that miR-155 is upregulated in both M1-polarized macrophages and microglia. Experimentally, exosomal transfer of miR-155 participated in M1-BMDMs-induced EndoMT and mitochondrial ROS generation in bEnd.3 cells, and subsequently activated the NF-κB signaling pathway by targeting downstream suppressor of cytokine signaling 6 (SOCS6), and suppressing SOCS6-mediated p65 ubiquitination and degradation. Finally, a series of rescue assay further verified that exosomal miR155/SOCS6/p65 axis regulated the EndoMT process and mitochondrial function in vascular endothelial cells. In summary, our work revealed a potential mechanism describing the communications between macrophages and vascular endothelial cells after SCI which could benefit for future research and aid in the development of potential therapies for SCI.

Application of low-nickel stainless steel anchor was one of the economical and effective methods to solve the durability problem of slope engineering. At present, there are scarce reports about corrosion characteristics of low-nickel stainless steel in various underground waters. For investigating the corrosion initiation of stainless steel anchor bolt in corrosive underground water, the effect of SO42−, HCO3− and pH value on the corrosion behavior of 201 low-nickel stainless steel was studied via electrochemical methods. As the SO42− concentration, HCO3− concentration or pH value increase, the open circuit potential and polarization resistance increase, while the double-layer capacitance, donor density and passive current density decrease. The results indicate that corrosion is inhibited by SO42−, HCO3− and OH− in underground water. In addition, the inhibitive efficiency of SO42− and HCO3− increases with the SO42− and HCO3− concentration.

This paper presents the fabrication of a low-loss optical waveguide at 1310 nm on an optical printed circuit board. UV lithography and low-loss UV curable polymer material (ZPU-RI) is used for the fabrication. The experimental results show that minimal optical loss is 0.42 dB/cm as the waveguide length is 3.8 cm.

We quantify methane emissions and their 2010–2017 trends by sector in the contiguous United States (CONUS), Canada, and Mexico by inverse analysis of in situ (GLOBALVIEWplus CH4 ObsPack) and satellite (GOSAT) atmospheric methane observations. The inversion uses as prior estimate the national anthropogenic emission inventories for the three countries reported by the US Environmental Protection Agency (EPA), Environment and Climate Change Canada (ECCC), and the Instituto Nacional de Ecologia y Cambio Climatico (INECC) in Mexico to the United Nations Framework Convention on Climate Change (UNFCCC), and thus serves as an evaluation of these inventories in terms of their magnitudes and trends. Emissions are optimized with a Gaussian mixture model (GMM) at 0.5° × 0.625° resolution and for individual years. Optimization is done analytically using log-normal error forms. This yields closed-form statistics of error estimates and information content on the posterior (optimized) estimates, allows better representation of the high tail of the emission distribution, and enables construction of a large ensemble of inverse solutions using different observations and assumptions. We find that GOSAT and in situ observations are largely consistent and complementary in the optimization of methane emissions for North America. Mean 2010–2017 anthropogenic emissions from our base GOSAT + in situ inversion, with ranges from the inversion ensemble, are 36.9 (32.5–37.8) Tg a−1 for CONUS, 5.3 (3.6–5.7) Tg a−1 for Canada, and 6.0 (4.7–6.1) Tg a−1 for Mexico. These are higher than the most recent reported national inventories of 26.0 Tg a−1 for the US (EPA), 4.0 Tg a−1 for Canada (ECCC), and 5.0 Tg a−1 for Mexico (INECC). The correction in all three countries is largely driven by a factor of 2 underestimate in emissions from the oil sector with major contributions from the south-central US, western Canada, and southeast Mexico. Total CONUS anthropogenic emissions in our inversion peak in 2014, in contrast to the EPA report of a steady decreasing trend over 2010–2017. This reflects combined effects of increases in emissions from the oil and landfill sectors, decrease from the gas, and flat emissions from the livestock and coal sectors. We find decreasing trends in Canadian and Mexican anthropogenic methane emissions over the 2010–2017 period, mainly driven by oil and gas emissions. Our best estimates of mean 2010–2017 wetland emissions are 8.4 (6.4–10.6) Tg a−1 for CONUS, 9.9 (7.8–12.0) Tg a−1 for Canada, and 0.6 (0.4–0.6) Tg a−1 for Mexico. Wetland emissions in CONUS show an increasing trend of 2.6 (1.7–3.8) % a−1 over 2010–2017 correlated with precipitation.

In this paper, a transparent and flexible absorber using graphene is presented, in which the frequency of the resonant absorption can be modulated in Ku band. The proposed absorber contains a four-layer structure including the patterned graphene capacitor, the periodical striper layer, the polydimethylsiloxane (PDMS) layer and a metallic wire grid ground. By tuning the bias voltage applying to the graphene capacitor, the resonance frequency can be dynamically and continuously shifted from 16.7GHz to 14.6GHz according to the experimental measurement. The optically transparent and structurally flexible characteristics provide more flexibility for applications in electromagnetic stealth and electromagnetic protection of transparent optical components.

Background: Almost all patients with lung adenocarcinoma (LUAD) develop resistance to EGFR-TKIs, which limit the long-term clinical application of these agents. Accumulating evidence shows one of the main reasons for resistance to EGFR-TKIs is induction of autophagy in tumor cells. Our previous study found that circumsporozoite protein (CSP) in Plasmodium can suppress autophagy in host hepatocytes. However, it is unknown whether CSP-mediated inhibition of autophagy could improve the anti-tumor effect of EGFR-TKIs. Methods: We constructed A549 and H1975 cell lines with stable overexpression of CSP (OE-CSP cells). CCK-8, LDH, flow cytometry, and colony analysis were performed to observe the effect of CSP overexpression on cell viability, the apoptosis rate, and stemness. The sensitizing effect of CSP on gefitinib was evaluated in vivo using a subcutaneous tumor model in nude mice and immunohistochemical assay. The role of CSP in regulation of autophagy was investigated by laser confocal microscopy assay and Western blotting. A transcriptome sequencing assay and real-time polymerase chain reaction were used to determine the levels of mRNA for autophagy-related proteins. Cyclohexane, MG132, TAK-243, and immunoprecipitation assays were used to detect and confirm proteasomal degradation of LC3B. Results: OE-CSP A549 and H1975 cells were more sensitive to gefitinib, demonstrating significant amounts of apoptosis and decreased viability. In the OE-CSP group, autophagy was significantly inhibited, and there was a decrease in LC3B protein after exposure to gefitinib. Cell viability and stemness were recovered when OE-CSP cells were exposed to rapamycin. In nude mice with xenografts of LUAD cells, inhibition of autophagy by CSP resulted in suppression of cell growth and more marked apoptosis during exposure to gefitinib. CSP promoted ubiquitin-proteasome degradation of LC3B, leading to inhibition of autophagy in LUAD cells after treatment with gefitinib . When LUAD cells were treated with the ubiquitin-specific inhibitor TAK-243, cell viability, apoptosis, and growth were comparable between the OE-CSP group and a control group both in vivo and in vitro . Conclusions: CSP can inhibit gefitinib-induced autophagy via proteasomal degradation of LC3B, which suggests that CSP could be used as an autophagy inhibitor to sensitize EGFR-TKIs.

Arbuscular mycorrhizal fungi regulated the distribution of nitrogen in the leaves, thereby facilitating the adaptation of the endangered plant Torreya jackii to a low-nitrogen environment. Rhizophagus irregularis was inoculated into sterilized soil to investigate its impact on the distribution ratio of leaf nitrogen in cell wall proteins, cell membrane proteins, water-soluble proteins, and photosynthetic systems which includes the carboxylation system (PC), energy metabolism (PB), and light-harvesting system in the endangered species Torreya jackii. The results showed that R. irregularis reduced the specific leaf weight and the distribution ratio of nitrogen in cell wall proteins in the leaves of T. jackii, whereas it enhanced the distribution ratio of nitrogen in cell membrane proteins and water-soluble proteins. R. irregularis enabled more nitrogen uptake for growth by decreasing the distribution of nitrogen to the structural substances. At low-nitrogen levels, inoculation with R. irregularis improved the plant height (18.78 ~ 36.04%), shoot dry weight (50.53 ~ 64.33%), total dry weight (42.86 ~ 52.82%), maximal net photosynthetic rate (Pmax) (16.83 ~ 20.11%), photosynthetic nitrogen use efficiency (PNUE) (40.01 ~ 43.14%), PC (33.56 ~ 38.59%) and PB (29.08 ~ 34.02%). However, it did not substantially affect the leaf nitrogen content per unit area or the leaf nitrogen content per unit mass. Moreover, Pmax exhibited a significant positive correlation with PC and PB, and all three parameters showed a significant positive correlation with the PNUE, thereby revealing that R. irregularis increased the photosynthetic capacity and PNUE of T. jackii through boosting PC and PB.

Omega‑3 polyunsaturated fatty acids (n‑3 PUFAs) exert a negative effect on IL‑6 production in several liver disorders, including cirrhosis, acute liver failure and fatty liver disease. However, its effect on the production of IL‑11, another important IL‑6 family cytokine, remains unclear. IL‑11 was found to be significantly elevated in acetaminophen (APAP)‑induced liver damage. The aim of the present study was to investigate whether and how n‑3 PUFAs modulate IL‑11 production during APAP‑induced liver injury. For that purpose, wild‑type (WT) and fat‑1 transgenic mice were intraperitoneally injected with APAP to induce liver injury. Serum was collected for ELISA and alanine aminotransferase assay. The hepatocytes of APAP‑injected mice were isolated for reverse transcription‑quantitative PCR and western blot analyses. For the in vitro study, primary hepatocytes isolated from WT or fat‑1 mice were stimulated with APAP. The results revealed that both endogenous and exogenous n‑3 PUFAs significantly aggravated APAP‑induced liver damage via the downregulation of STAT3 signaling. Notably, n‑3 PUFAs inhibited IL‑11 expression, but not IL‑6 expression in hepatocytes during the APAP challenge. Furthermore, it was demonstrated that limited phosphorylation of ERK1/2 and Fos‑​like‑1 (Fra‑1) expression are responsible for the n‑3 PUFA‑mediated inhibitory effect on IL‑11 production in APAP‑treated hepatocytes. It was concluded that n‑3 PUFAs inhibit IL‑11 production and further STAT3 activation in hepatocytes during APAP‑induced liver injury. Therefore, ERK1/2‑mediated Fra‑1 expression is responsible for the effect of n‑3 PUFAs on IL‑11 expression.

The study aimed to compare the efficacy and safety of all-trans retinoic acid (ATRA) plus low-dose rituximab (LD-RTX) with LD-RTX monotherapy in corticosteroid-resistant or relapsed immune thrombocytopenia (ITP) patients. Recruited patients were randomized at a ratio of 2:1 into 2 groups: 112 patients received LD-RTX plus ATRA, and 56 patients received LD-RTX monotherapy. Overall response (OR), defined as achieving a platelet count of ≥30 × 109/L confirmed on ≥2 separate occasions (≥7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment, and the absence of bleeding within 1 year after enrollment, was observed in more patients in the LD-RTX plus ATRA group (80%) than in the LD-RTX monotherapy group (59%) (between-group difference, 0.22; 95% CI, 0.07-0.36). Sustained response (SR), defined as maintenance of a platelet count >30 × 109/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR during 1 year following enrollment, was achieved by 68 (61%) patients in the combination group and 23 (41%) patients in the monotherapy group (between-group difference, 0.20; 95% CI, 0.04-0.35). The 2 most common adverse events (AEs) for the combination group were dry skin and headache or dizziness. Our findings demonstrated that ATRA plus LD-RTX significantly increased the overall and sustained response, indicating a promising treatment option for corticosteroid-resistant or relapsed adult ITP. This study is registered at www.clinicaltrials.gov as #NCT03304288.

The aberrant release of endoplasmic reticulum (ER) calcium leads to the disruption of intracellular calcium homeostasis, which is associated with the occurrence of ER stress and closely related to the pathogenesis of liver damage. Mannan-binding lectin (MBL) is a soluble calcium-dependent protein synthesized primarily in hepatocytes and is a pattern recognition molecule in the innate immune system. MBL deficiency is highly prevalent in the population and has been reported to be associated with susceptibility to several liver diseases. We here showed that genetic MBL ablation strongly sensitized mice to ER stress-induced liver injury. Mechanistic studies established that MBL directly interacted with ER-resident chaperone immunoglobulin heavy chain binding protein (BiP), and MBL deficiency accelerated the separation of PKR-like ER kinase (PERK) from BiP during hepatic ER stress. Moreover, MBL deficiency led to enhanced activation of the PERK-C/EBP-homologous protein (CHOP) pathway and initiates an inositol 1,4,5-trisphosphate receptor (IP3R)-mediated calcium release from the ER, thereby aggravating the hepatic ER stress response. Our results demonstrate an unexpected function of MBL in ER calcium homeostasis and ER stress response, thus providing new insight into the liver injury related to ER stress in patients with MBL deficiency.

For electrochemical nitrogen reduction reaction (NRR), hybridizing transition metal (TM) compounds with nitrogen-doped carbonaceous materials has been recognized as a promising strategy to improve the activity and stability of electrocatalysts due to the synergistic interaction from the TM-N-C active sites. Nevertheless, up to date, the fundamental mechanism of this so-called synergistic electrocatalysis for NRR is still unclear. Particularly, it remains ambiguous which configuration of N dopants, either pyridinic N or pyrrolic N, when coordinated with the TM, predominately contributes to this synergy. Herein, a self-assembled three-dimensional 1T-phase MoS2 microsphere coupled with N-doped carbon was developed (termed MoS2/NC), showing an impressive NRR performance in neutral medium. The hybridization of MoS2 and N-doped carbon can synergistically enhance the NRR efficiency by optimizing the electron transfer of catalyst. Acidification/blocking/poisoning experiments reveal the decisive role of pyridinic-N-Mo bonding, rather than pyrrolic-N-Mo bonding, in synergistically enhancing NRR electrocatalysis. The electrochemical-based in situ Fourier transform infrared spectroscopy (in situ FTIR) technology provides deep insights into the substantial contribution of pyridinic-N-MoS2 sites to NRR electrocatalysis and further uncover the underlying mechanism (associative pathway) at a molecular level.

ObjectiveWe evaluated swine and bovine pulmonary visceral pleura (PVP) in artery patch-angioplasty in swine model of high-fat diet.BackgroundArterial patch-angioplasty is frequently used for repair or reconstruction of arteries. An autologous patch is often limited by the number and dimension of donor tissue and can result in donor complications. Furthermore, mechanical mismatch is a cause of poor performance of vascular reconstruction. Here, we introduce a readily available patch biomaterial with similar compliance as native arteries.MethodsThe PVP was peeled from swine and bovine lungs by hydro-dissection. The swine and bovine PVPs were crosslinked with glutaraldehyde and then sterilized. The swine PVP (sPVP) patches were implanted in the carotid and femoral arteries of six Yorkshire pigs that were fed a regular diet and euthanized at 2 and 4 months postoperative. The bovine PVP (bPVP) patches were implanted in the carotid artery of six Yucatan pigs that were fed a high-fat diet and euthanized at 4 months postoperative. Patency was evaluated by ultrasound and angiography. Neo-endothelium and media were evaluated by histologic examination.ResultsAll arteries in patch-angioplasties remained patent with no adhesions, inflammation, or aneurysms. Biomarkers of endothelial cells (e.g., Factor VIII and eNOS) were detected in the neo-endothelial cells. We observed endothelial cell–cell junctions in the confluent neo-endothelium in the PVP patches. Neo-media composed of vascular smooth muscle developed similar as native arteries. In the hypercholesterolemic model, we observed the accumulation of cholesterol in both arterial tissues and in the neo-vascular tissues in the PVP patches. Protein expressions of lipid transport and metabolism (e.g., APOE-1, ABCA, and PACK9) were also observed in both arterial and neo-vascular tissues.ConclusionThe PVP patch-angioplasty overcomes the pitfalls of compliance mismatch of synthetic patches and has a non-thrombogenic surface. The proliferation of vascular cells assembled to generate the neo-endothelium and media in the patch-angioplasties to support long-term patency. The neo-vascular tissue in PVP patch-angioplasty also developed similar cellular functions for lipid transport and metabolism compared with native arteries in hypercholesterolemia.

In this paper, considering the porosity defects of Additive Manufacturing (AM), a level set topology optimization method for AM with porosity constraints is proposed. The concept of topological sensitivity is used to formulate a global porosity constraint function in the proposed method, and a level set topology optimization model considering porosity defects is obtained. To improve the robustness of the algorithm, the topology optimization model is solved in two phases. At first, the classical level set method without the porosity constraint is used to initially optimize the structure. During this process, the hole nucleation method combining bi-directional evolutionary structural optimization (BESO) and the topological sensitivity is used. Secondly, the topology optimization considering the effects of porosity is implemented on the preliminary optimization results. After performing the two-step optimization, a robust structure that alleviates the harmful impact of porosity defects is obtained. Finally, the robustness and effectiveness of the proposed method are validated by several two-dimensional numerical examples.

Intestinal mucositis is a common side effect of anticancer regimens that exerts a negative impact on chemotherapy. Superoxide dismutase (SOD) is a potential therapy for mucositis but efficient product is not available because the enzyme is degraded following oral administration or induces an immune reaction after intravascular infusion. Multi-modified Stable Anti-Oxidant Enzymes® (MS-AOE®) is a new recombinant SOD with better resistance to pepsin and trypsin. We referred it as MS-SOD to distinguish from other SODs. In this study we investigated its potential to alleviate 5-FU-induced intestinal injury and the mechanisms. An intestinal mucositis model was established in C57/BL6 mice by 5-day administration of 5-FU (50 mg/kg every day, ip). MS-SOD (800 IU/10 g, ig) was given once daily for 9 days. 5-FU caused severe mucositis with intestinal morphological damage, bodyweight loss and diarrhea; MS-SOD significantly decreased the severity. 5-FU markedly increased reactive oxygen species (ROS) and inflammatory cytokines in the intestine which were ameliorated by MS-SOD. Furthermore, MS-SOD modified intestinal microbes, particularly reduced Verrucomicrobia, compared with the 5-FU group. In Caco2 cells, MS-SOD (250–1000 U/mL) dose-dependently decreased tBHP-induced ROS generation. In RAW264.7 cells, MS-SOD (500 U/mL) had no effect on LPS-induced inflammatory cytokines, but inhibited iNOS expression. These results demonstrate that MS-SOD can scavenge ROS at the initial stage of injury, thus play an indirect role in anti-inflammatory and barrier protein protection. In conclusion, MS-SOD attenuates 5-FU-induced intestinal mucositis by suppressing oxidative stress and inflammation, and influencing microbes. MS-SOD may exert beneficial effect in prevention of intestinal mucositis during chemotherapy in clinic.

The accelerated corrosion behavior of copper T2 and brass H62 exposed in simulated Nansha marine atmosphere for different periods were investigated by weight loss method, SEM, XRD and potentiodynamic polarization measurements. The results indicate that copper T2 and brass H62 underwent severe corrosion, and the final corrosion rates at 32 days of exposure were 0.24 μm/d and 0.10 μm/d, respectively. Moreover, the overall corrosion type of copper T2 was uniform and the corrosion products Cu2O and Cu2Cl(OH)3 played a vital role in the corrosion rate of copper. While the dezincification corrosion with zinc preferential dissolution was obvious in brass H62. The predominant phases were the zinc-rich compounds Zn5(OH)8Cl2·H2O, Zn12(SO4)3Cl3(OH)15·5H2O and NaZn4(SO4)Cl(OH)6·6H2O. There existed a large number of copper-rich holes with 20–50 μm depth beneath the corrosion product layer.